This invention relates generally to chemical sensors, and more particularly, to a catheter-type potentiometric gas sensor suitable for continuous in vivo blood gas monitoring.
The knowledge of gas levels in blood is essential for the accurate assessment of the respiratory and acid-base status of a patient. Oxygen and carbon dioxide, the respiratory gases, are of fundamental importance since their partial pressures, pO.sub.2 and pCO.sub.2, are useful in determining cardiopulmonary homeostasis, or the ability of the cardiopulmonary system to maintain a delicate balance between the body's respiratory CO.sub.2 production and its O.sub.2 consumption. Additionally, the partial pressure of carbon dioxide in blood and the dissolved bicarbonate anion are the two principle factors which govern the pH of the blood. The measurement of two of these three parameters, such as pH and partial pressure of carbon dioxide, will completely characterize the acid-base state of the blood.
Commercially available blood gas analyzer systems typically monitor three analytes, including blood pH, the partial pressure of carbon dioxide, and the partial pressure of oxygen. Such monitoring provides a clinician with a complete determination of the respiratory and acid-base status of a patient.
In conventional discrete blood gas analyzers, the partial carbon dioxide pressure level in blood is most commonly obtained by drawing a discrete arterial blood sample which is then analyzed by a conventional Severinghaus carbon dioxide sensor housed in an automated blood gas analyzer. At least a two to three minute time lag between the drawing of a sample and the recording of the value of the partial pressure of carbon dioxide, is inherent in the known discrete sampling arrangement. However, in many diagnostic situations, such as emergency, surgical, and critical care patients, blood gas levels can change abruptly, illustratively within minutes, thereby indicating eminent respiratory or metabolic failure. In such situations, a clinician working with a discrete blood gas analyzer is required to make frequent blood gas measurements so as to diagnose accurately the patient's rapidly changing condition. Thus, a major disadvantage of the known method is the high expense associated with the maintenance of a sufficient number of blood gas analyzers, and the providing of a staff of trained personnel to perform the frequent blood gas measurements. More importantly, improper collection and/or handling of a blood sample prior to analysis can produce error in the discrete blood gas determination. It is evident from the foregoing that the time lag which is inherent in the discrete sampling system limits the speed of diagnosis, and consequently the implementation of corrective treatment. Accordingly, intensive research has been conducted over the past decade, devoted to the search for methods which allow for the continuous monitoring of arterial blood gas tensions.
A variety of technologies has been applied to the development of continuous blood sensors for the partial pressure of carbon dioxide. The monitoring of partial pressures of carbon dioxide can involve invasive and noninvasive approaches. Conventional gas sensors have been used in noninvasive extracorporeal loops and transcutaneous arrangements. Invasive gas sensing probes have been based on mass spectrometry, conductivity, gas chromatography, potentiometry, and fiber optic systems. Although each of these developments has some merit, none has achieved wide clinical application.
One prior art system is an extracorporeal loop device which continuously draws arterial blood which is then circulated through appropriate tubing to external sensing devices; the blood then being returned to a vein elsewhere in the body of the patient. Typically, the external sensing devices incorporate sensors for oxygen, carbon dioxide, and pH measurements. It is a problem with all extracorporeal systems that the patient must be heparinized to prevent blood clotting in the loop or on the sensors, and to prevent loose blood clots from causing vascular occlusion or strokes. Heparinization increases the risk of post-operative complications in surgical patients since necessary clotting mechanisms are inhibited. Additional drawbacks of extracorporeal devices include losses of carbon dioxide in the loop tubing, the need for elaborate temperature control, and the increased risk of infection. Consequently, extracorporeal loops are rarely used for blood gas measurements.
Non-invasive transcutaneous blood gas sensors were developed in the early 1970's In this known system, heated conventional gas sensors are placed directly on the skin of the patient such that the partial pressure of gases diffusing to the skin surface can be measured. This diffusion of gases from the subcutaneous arteries to the skin surface is dependent upon skin thickness, blood flow, tissue concentration and/or expiration, and arterial gas concentration. In infants, the factors balance, such that the transcutaneous blood gas values approximate the arterial values. There is, however, a wide variation in adult skin thickness which leads to incorrect predictions of arterial blood gas levels from transcutaneous measurements. Inaccurate predictions of arterial blood gas levels will also occur in patients with reduced blood flow from injury or illness. Thus, transcutaneous blood gas monitoring is clinically accepted for infants, but rarely is applied to adults.
A known invasive system involves in vivo mass spectrometric blood gas analysis. This system was first proposed in 1966 and has since been pursued by a number of researchers. The basic configuration requires the use of a mass spectrometer, an in vivo sampling probe, and associated connecting tubing. A significant limitation of this technique is the complexity and cost of mass spectrometer instrumentation relative to that of electrochemical sensors. The major drawback to mass spectrometric probe measurements is the non-equilibrium flow dependent, or diffusion limited nature of the gas sampling probe. The mass spectrometer maintains the sampling probe at a negative pressure that withdraws gases from the surrounding blood stream. Under low blood flow conditions, the extraction of gases by the probe may deplete the adjacent blood of analyte causing erroneously low results. Moreover, blood clotting and/or protein build-up on the probe can impede the diffusion of gases into the probe, thereby yielding false blood gas values. Thus, economic factors and non-equilibrium sampling effects account for the limited biomedical application of mass spectrometric blood gas analysis.
Similarly, flow dependent conductivity-based carbon dioxide catheters have been described for in vivo applications. These catheters, however, are non-selective and suffer the same non-equilibrium disadvantages as the mass spectrometric probes. Gas chromatography has also been applied to continuous blood gas monitoring. Blood gases diffuse into the body of an indwelling catheter probe where they approach their equilibrium concentration with a bolus of carrier gas (He) contained therewithin. At fixed intervals, illustratively between three and four minutes, the bolus is flushed through the gas analyzer unit for separation and measurement. Thus, the gas chromatographic probes do not sample continuously, but rather an automated analysis is performed every four minutes. The disadvantages of this approach include the delicate nature of the probe and its associated high failure rate. More importantly, a commercial implementation of this approach will yield serious inaccuracies, on the order of between 10 and 20 per cent, in blood gas determinations.
In recent years, fiber optic carbon dioxide sensors have been developed. This approach offers several advantages including true equilibrium measurements of partial carbon dioxide, lack of electrical connections to the patient, and ease of miniaturization of fiber optic devices. Despite the promise of fiber optic designs, difficulties with sensor drift appear to have limited its utility in vivo applications in measuring the partial pressure of carbon dioxide. The drift has been attributed to changes in optical path length caused by deformation of the sensor tip while it is in the blood vessel.
The development of intravascular electro-based probes for the measurement of partial pressure of carbon dioxide has centered primarily on the miniaturization of the known Severinghaus sensor. FIG. 1 is a comparative schematic representation of Severinghaus-type ammonia (NH.sub.3) and carbon dioxide (CO.sub.2) gas sensors. As shown in the drawing, sodium sensor 10 and carbon dioxide sensor 11 are each combination electrodes in that they monitor pH levels also. Each of the sensors is provided with a respective one of pH electrodes 12 and 13. Electrode 12 is filled with NH.sub.3 and electrode 13 is filled with carbon dioxide. Such electrodes are arranged in an internal electrolyte and are separated therefrom by respective glass membranes 14 and 15. A gas permeable membrane separates the internal electrolyte from the substance being monitored, illustratively blood (not shown).
Since Severinghaus sensors are potentiometric devices, measurements are made essentially under zero-current conditions so that no analyte carbon dioxide is consumed by the measurement process. Thus, true equilibrium measurements are made and problems associated with mass transfer of carbon dioxide, such as blood flow variations and carbon dioxide diffusion limitations, should not cause errors in the partial pressure values of carbon dioxide which are determined. In addition, all Severinghaus-type carbon dioxide devices are unaffected by anaesthetic gases.
The design of the system of FIG. 1 employs miniaturized glass pH electrodes as internal sensing elements in catheter size devices. However, such arrangements are hampered by the fragility, noise, and cost associated with the electrodes. The prior art has thrust at the problem associated with miniature glass electrodes, by providing sensors which detect the partial pressure of carbon dioxide based on quinhydrone and antimony pH sensitive electrode systems. These sensors, however, suffer from the disadvantages of oxygen sensitivity, instability, and large size. Thus, they do not appear to be suitable for in vivo testing.
FIG. 2 is a schematic representation of a prior art combination sensor 20 which monitors pH and the partial pressure of carbon dioxide. This known probe is comprised of a palladium oxide pH electrode 21, a Ag/AgCl reference electrode 22 and a bicarbonate electrolyte 23 housed behind a gas-permeable membrane 64 which contains a mobile hydrogen ion carrier which makes the membrane permeable to hydrogen ions. The partial pressure of carbon dioxide is measured by monitoring the voltage between the two internal electrodes, while the sample pH is measured between the Pd/PdO electrode 21 and an external reference electrode (not shown). Sensor 20 measures 0.9 mm in outside diameter. It is a disadvantage of this type of sensor that they are poorly flexible, exhibiting a decrease in sensitivity when the sensor is bent. This type of sensor also drifts unacceptably unless recalibrated every 1.5 hours. The drift is attributed to the PdO electrode's sensitivity to redox species. In addition, the sensor is also very sensitive to temperature changes, as might occur during fever or hypothermia. As a result of this, this combination sensor has seen only limited use.
FIG. 3 is a schematic representation of a catheter sensor 30 which measures the partial pressure of carbon dioxide and is based on a tubular polymeric membrane internal pH electrode. In this known arrangement, a pH sensitive membrane 31 is situated safely within the wall of the internal tubing, rather than at the vulnerable tip of the sensor. This protects the sensing regions from damage during catheter placement or removal. In addition, this geometry allows for sensor size reduction without a corresponding decrease in the pH sensitive membrane area and a concomitant increase in electrode resistance. Also noteworthy is the heightened rate of flexibility afforded by the polymer based internal pH electrode. Finally, since the internal electrode is based on a hydrogen ion permselective polymer membrane, the sensor is virtually insensitive to sample redox species.
Although this design is promising for continuous in vivo monitoring of the partial pressure of carbon dioxide, there are difficulties in its fabrication which will limit its application.
It is, therefore, an object of this invention to provide a simple and economical sensor which provides determination of the respiratory and acid-base status of a patient.
It is another object of this invention to provide an implantable sensor for continuous monitoring of blood carbon dioxide partial pressures.
It is also an object of this invention to provide a single catheter implant which can monitor pH and the partial pressure of carbon dioxide simultaneously.
It is additionally an object of this invention to provide a blood gas analyzer system which does not require trained personnel to be operated.
It is a further object of this invention to provide a blood gas analysis system which reduces the possibility of error resulting from faulty collection and/or handling of a blood sample.
It is still another object of this invention to provide a blood gas analysis sensor which eliminates lag time between samplings.
It is a yet further object of the invention to provide a blood gas monitoring arrangement which eliminates the need to heparinize a patient.
it is also a further object of this invention to provide a blood gas sensor which is not plagued by drift.
It is yet another object of this invention to provide a blood gas sensor which is not fragile and does not have a high failure rate.